20-9611951-T-C

Variant names:

• chr20-9611951-T-C
• rs6056754
• NM_177990.4:c.205-31021A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177990.4(PAK5):​c.205-31021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,008 control chromosomes in the GnomAD database, including 32,242 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (32242 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 2 publications found

Genes affected

PAK5 (HGNC:15916): (p21 (RAC1) activated kinase 5) The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP. This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.205-31021A>G		intron_variant	Intron 3 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.205-31021A>G		intron_variant	Intron 3 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.205-31021A>G		intron_variant	Intron 4 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.205-31021A>G		intron_variant	Intron 4 of 10	1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96152 AN: 151890 Hom.: 32195 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.633 AC: 96263 AN: 152008 Hom.: 32242 Cov.: 32 AF XY: 0.625 AC XY: 46419 AN XY: 74274

African (AFR) AF: 0.861 AC: 35748 AN: 41514

American (AMR) AF: 0.563 AC: 8595 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2424 AN: 5148

South Asian (SAS) AF: 0.355 AC: 1706 AN: 4800

European-Finnish (FIN) AF: 0.557 AC: 5870 AN: 10546

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38199 AN: 67942

Other (OTH) AF: 0.596 AC: 1258 AN: 2112

Alfa AF: 0.582 Hom.: 12080

Bravo AF: 0.650

Asia WGS AF: 0.478 AC: 1661 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6056754; hg19: chr20-9592598;